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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2023
    In:  Surgical Oncology Clinics of North America Vol. 32, No. 4 ( 2023-10), p. 663-673
    In: Surgical Oncology Clinics of North America, Elsevier BV, Vol. 32, No. 4 ( 2023-10), p. 663-673
    Type of Medium: Online Resource
    ISSN: 1055-3207
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e13096-e13096
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13096-e13096
    Abstract: e13096 Background: Breast cancers remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive potential are believed to be the major contributors of these outcomes. Triple-negative breast cancer (TNBC) are notoriously aggressive, difficult-to-treat, and metastatic. Inflammation-driven tumorigenesis has been shown to correlate with cell-free DNA (cfDNA) and other damage-associated molecular patterns (DAMPs) in cancer patient sera. We showed that nucleic-acid scavengers (NAS) can block pro-inflammatory signals elicited by DAMP-activation of innate immune sensors (e.g. toll-like receptors). Treatment with the NAS PAMAM-G3 drastically reduced liver metastatic burden in an immunocompetent murine model of pancreatic cancer. Methods: TNBC cells lines were treated with a cocktail of standard-of-care chemotherapeutic agents and the conditioned media (CM) from these cells served as an in vitro DAMP source. Downstream function of TLR activation was tested via a HEK293-TLR reporter cell line measuring absorbance at 655nm. The in vitro invasive phenotype was tested and quantified using a Transwell-Matrigel invasion assay. Cytokine secretion was measured using a BioLegend cytokine array. Results: TNBC CM greatly increased TNBC cell invasion in vitro and that treatment with the NAS PAMAM-G3 significantly inhibits this effect. Treatment of human monocytes (THP-1) with TNBC CM elicited a strong pro-inflammatory response with elevated levels of IL-8, IL-6, CCL2, and IL-1β. Other biologically immune responders including human PBMCs will be tested to determine the potential impact on the tumor immune microenvironment during tumorigenesis and treatment. Conclusions: To elucidate the mechanism by which this NAS works in these tumor settings, our lab has developed several PAMAM-G3 derivatives, including biotin, IR-, and near-IR fluorophore labeled molecules. These molecules will allow us to capture and characterize DAMPs and do in vivo live imaging experiments to gain insight into NAS PK/PD properties. This insight into NAS capabilities will enhance our understanding of metastatic progression and its interplay with the immune system. Moreover, these principles will aid in the development of novel of anti-metastatic therapies to improve TNBC patient outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS616-TPS616
    Abstract: TPS616 Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer (IBC). However, over 97% of women are currently treated with surgery +/- radiation. An alternative to surgery is active monitoring (AM), a management approach in which mammograms/physical exams are used to monitor breast changes and determine when, or if, surgery is needed. The COMET Study will compare risks and benefits of AM versus surgery for low-risk DCIS in the setting of a Phase III multicenter prospective randomized trial. The study is funded by the Patient-Centered Outcomes Research Institute. The COMET trial opened in the U.S. in June 2017 (Clinicaltrials.gov reference: NCT02926911). In November 2021, the Data Safety Monitoring Board reviewed the trial and suggested that it continue as planned. Patient accrual will continue until 12/31/2022. Methods: The primary objective is to assess whether the 2-year ipsilateral IBC rate for AM is non-inferior to that for surgery. Secondary objectives include determining whether AM is non-inferior to surgery for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at baseline, 6-months, and years 1-5. Eligibility criteria include: age 〉 40 at diagnosis; pathologic confirmation of grade I/II DCIS or atypia verging on DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; no mass on physical exam or imaging. The accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites. Sample size is estimated using a 2-group test of non-inferiority of proportions, with the 2-year IBC rate in the surgery group assumed to be 0.10 based on published studies and non-inferiority margin of 0.05. Based on a 1-sided un-pooled z-test, with alpha = 0.05, a sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. Final analysis plan will include a per protocol component as well as a pragmatic component for patients who are randomized and decline participation in their assigned arm. Primary analyses will adjust for dropout, non-compliance and contamination by utilizing instrumental variable methods. Clinical trial information: NCT02926911.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 6512-6512
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 6512-6512
    Abstract: 6512 Background: National tumor registries, such as the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, and End Results Program), have been used to explore numerous research questions related to trends in disease incidence, treatment patterns, and outcomes. However, some have criticized that they may not fully represent the general population. As such, we sought to compare the incident breast cancer cases in the NCDB and SEER to a national population cancer registry. Methods: All patients diagnosed with malignant or in situ breast cancer 2010-2019 were selected from the NCDB (Fall 2022 release) and SEER-22 (November 2021 release) and compared to breast cancer patient counts from the US Cancer Statistics Public Use Database (USCS, 2021 submission). Patient frequencies were summarized by age, sex, race/ethnicity, and year of diagnosis. Percent case coverage was estimated as the number of patients in the NCDB or SEER divided by the number of patients in the USCS. Chi-square tests were used to compare patient counts across data sources. Results: In total, the USCS database reported 3,047,509 patients diagnosed with breast cancer between 2010-2019, of which, 77.5% (N=2,362,477) were included in the NCDB and 46.0% (N=1,403,272) in SEER. Over time, case coverage steadily improved for the NCDB (72.8% in 2010 to 81.5% in 2019), while only a minor increase was observed in SEER (46.0% in 2010 to 46.6% in 2019). When compared to the USCS, case ascertainment was notably lower for individuals age ≥50 in both the NCDB and SEER (both p 〈 0.001). The overwhelming majority of patients were captured by the NCDB (age 〈 50: 81.7%; age ≥50: 76.6%) while SEER identified approximately half (age 〈 50: 49.4%; age ≥50: 45.3%). Case ascertainment also varied significantly by patient sex across registries (both p 〈 0.001). For male breast cancers, 84.1% were captured in the NCDB, only 77.5% of female patients were included. In contrast, case coverage in SEER was better for females than males (46.1% vs 43.5%). Notably, registries varied significantly by race/ethnicity (both p 〈 0.001). Case coverage in the NCDB was highest for non-Hispanic White (78.2%), non-Hispanic Black (77.7%), and non-Hispanic Asian or Pacific Islander (72.5%) patients, and it was lowest for Hispanic (56.4%) and non-Hispanic American Indian/Alaska Native (41.1%). In SEER, case coverage was highest for non-Hispanic Asian or Pacific Islander (78.1%) and Hispanic (69.6%) patients, and it was considerably lower for all other subgroups (non-Hispanic Black 44.8%, non-Hispanic White 42.4%, and non-Hispanic American Indian/Alaska Native 36.6%). Conclusions: National US tumor registries provide data for a large sampling of breast cancer patients, and case coverage has improved over time. However, significant differences in case coverage were observed based on age, sex, and race/ethnicity, suggesting that analyses using these data sets should be interpreted with caution.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Institute of Electrical and Electronics Engineers (IEEE) ; 2020
    In:  IEEE Transactions on Biomedical Engineering Vol. 67, No. 6 ( 2020-6), p. 1565-1572
    In: IEEE Transactions on Biomedical Engineering, Institute of Electrical and Electronics Engineers (IEEE), Vol. 67, No. 6 ( 2020-6), p. 1565-1572
    Type of Medium: Online Resource
    ISSN: 0018-9294 , 1558-2531
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    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2020
    detail.hit.zdb_id: 2021742-0
    detail.hit.zdb_id: 2571926-9
    detail.hit.zdb_id: 2561637-7
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 6516-6516
    Abstract: 6516 Background: Due to the elevated risk of ipsilateral invasive breast cancer (iIBC) after diagnosis with primary ductal carcinoma in situ (DCIS), professional guidelines recommend surveillance screening within 6-12 months (mo) after completion of initial local treatment and annually thereafter. To characterize adherence to these guidelines, we explored longitudinal patterns of utilization and factors associated with the use of surveillance imaging (mammography, MRI, ultrasound) for women with primary DCIS treated with breast conserving surgery (BCS) ± radiotherapy (RT) within 6 mo of diagnosis. Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-15 was selected from 1,330 Commission on Cancer-accredited facilities (up to 20/site) in the US. All imaging exams coded as asymptomatic were collected from 6 mo up to 10 years (yr) post-diagnosis. Time was defined according to 12-mo long surveillance periods. To be included in a given surveillance period, women had to be alive and free of a new breast cancer diagnosis through the end of the period. Women were classified as “consistent” screeners if they had at least one surveillance screen during each period, for the first 5 yr post-treatment or until censoring, whichever occurred first. Repeated measures multivariable logistic regression with generalized estimating equations was used to model receipt of surveillance breast imaging over time. The model included clinical and socioeconomic features. Results: The final analytic cohort contained 12,559 women; 8,989 (71.6%) received RT after BCS. Median age was 60 yr (interquartile range: 52-69) and median follow-up was 5.6 yr (95% confidence interval [CI] 5.6-5.7). Among women who received BCS (instead of BCS+RT), 62.5% (79.7%) underwent surveillance imaging within 6-18 mo after diagnosis. 38.7% (54.0%) were categorized as “consistent” screeners. Compared to white women, Black women were less likely to rec eive surveillance screening after treatment for primary DCIS (odds ratio [OR] 0.85, 95% CI 0.77-0.94). Hispanic ethnicity had a similar association (OR 0.86, 95% CI 0.74-0.99) compared to non-Hispanic ethnicity. Women with private insurance, compared to government insurance, were more likely to receive screening (OR 1.20, 95% CI 1.11-1.30). Prognostic tumor features indicative of a higher risk of subsequent iIBC, including higher grade, presence of comedonecrosis, and hormone receptor-negative DCIS, were not associated with screening uptake. Conclusions: Despite guidelines recommending annual surveillance imaging, many women with primary DCIS do not undergo regular imaging after BCS. The findings from this US-based study suggest that disparities in screening uptake are associated with race/ethnicity and insurance status rather than prognostic tumor features.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 519-519
    Abstract: 519 Background: Most women diagnosed with ductal carcinoma in situ (DCIS) undergo surgical resection, potentially leading to overtreatment of patients who would not develop clinically significant breast cancer in the absence of locoregional treatment. We compared the risk of ipsilateral invasive breast cancer (iIBC) between DCIS patients who received breast conserving surgery (BCS) for their index diagnosis of DCIS (BCS group) and patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Excluding patients who received a mastectomy ≤6 months, the final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcome was the 8-year absolute difference in iIBC risk between BCS and SV; a subgroup analysis was performed for grade I/II patients. A propensity score (PS) model for treatment was fitted with sampling design (SD) weighting and random effects for patients within facilities. Absolute risk differences were estimated using PS-SD-weighted Kaplan Meier estimators. Results: Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with estrogen receptor-positive (80.6%), and nuclear grade I/II (54.5%) DCIS. The fraction of patients with a Charlson comorbidity score of ≥2 was higher in SV (14.2%) compared to BCS (6.4%, p 〈 0.001). The 8-year risk of iIBC was 3.0% (95% CI: 2.4%-3.6%) for BCS and 7.7% (95% CI: 4.9%-10.5%) for SV, with an absolute risk difference of 4.7% (95% CI: 4.5%-4.9%; log-rank p 〈 0.001). Among patients with grade I/II tumors, the 8-year risk of iIBC was 3.1% (95% CI: 2.3%-4.0%) for BCS and 6.1% (95% CI: 2.5%-9.8%) for SV; difference: 3.0% (95% CI: 2.7%-3.2%; p = 0.005). Conclusions: Despite an increased risk of iIBC in SV patients compared to BCS patients, the 8-year risk did not exceed 10% in either group. The risk of recurrence in BCS patients was comparable to previously reported estimates. These data demonstrate a considerable degree of overtreatment among patients with non-high grade DCIS. Prospective clinical trials will help determine the tradeoffs between universally directed as opposed to selectively applied surgery for low risk DCIS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 29_suppl ( 2020-10-10), p. 203-203
    Abstract: 203 Background: Previous studies have demonstrated an association between body mass index (BMI) and survival after breast cancer diagnosis, but the direction and strength of this relationship is inconsistent. Comorbidities that are more common in patients who are obese (BMI≥30) – including diabetes (DM), hypertension (HTN), and hyperlipidemia (HLD) – are often conflated with obesity with regard to their effects on breast cancer outcomes. We sought to determine the effect of BMI on overall survival (OS) among women with breast cancer after controlling for obesity-associated conditions. Methods: Women≥18y diagnosed with stage 0-IV breast cancer at an academic institution from Jan 2014-Jul 2016 and with known BMI at diagnosis were identified. χ 2 and ANOVA tests were used to compare intergroup differences. BMI was categorized as normal ( 〈 25), overweight (25-29.9), class 1 obesity (30-34.9), and class 2/3 obesity (≥35). Unadjusted OS by BMI class was estimated with the Kaplan-Meier method. Cox proportional hazards models were used to estimate the association of BMI with OS after adjusting for covariates including obesity-associated conditions. Results: 1027 patients were included (median follow-up 46.8 mos): 296 (28.9%) were overweight, 227 (22.1%) had class 1 obesity, and 207 (20.2%) had class 2/3 obesity. Non-Hispanic (NH) black women were overrepresented among obese patients, making up 25% (n=257) of all patients but 37.5% of obese patients. Rates of DM, HTN, and HLD increased with increasing BMI (all p 〈 0.01). Unadjusted OS differed significantly by BMI class, with overweight women having the worst 5-year OS (log-rank p=0.02). After adjustment, BMI continued to be associated with OS, with overweight women having significantly worse OS vs normal-weight women, but there was no significant association between obesity and OS (Table). Conclusions: Despite higher rates of DM, HTN, and HLD with increasing BMI, a diagnosis of obesity was not associated with worse OS in women with breast cancer but being overweight was, suggesting the need for a more nuanced understanding of body composition, obesity-associated conditions, and their respective potential impact on breast cancer outcomes. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 29_suppl ( 2020-10-10), p. 101-101
    Abstract: 101 Background: Overall breast cancer mortality in the US has declined since 1990, but racial/ethnic disparities have worsened. Since 1992, NC BCCCP has provided free/low-cost breast cancer screening to underserved women as part of a national effort by the Centers for Disease Control and Prevention (CDC) to mitigate these disparities. We sought to characterize and evaluate benchmarks for this previously unstudied, state-level cohort. Methods: We identified women ≥18y who underwent their first breast cancer screening via NC BCCCP from 2009-2018. Univariate analysis was used to compare differences in timeline of care and rates of breast pathology (i.e., cancer or atypia) by race/ethnicity and age. Logistic and negative binomial regression were used to identify factors associated with cancer diagnosis and time from enrollment to diagnosis (TTD) and treatment (TTT), respectively. Results: 88,893 women with complete records were identified (median age 50y, IQR 44-56): 45.5% were Non-Hispanic (NH) white, 30.9% NH black, 19.5% Hispanic, 1.7% American Indian (AI), and 1.1% Asian. Overall participation peaked in 2012 but steadily increased among Hispanic women over time (p 〈 0.001). Breast pathology was diagnosed in 2,016 (2.3%) women, with rates ranging from 1% in Hispanic women to 2.7% in NH whites. After adjustment, Hispanic women were least likely (vs NH white women: OR 0.40; 95% CI 0.34-0.47) to be diagnosed with breast cancer. Median TTD was 19d and TTT was 33d, both within the CDC’s 60d standard. In univariate analyses, women 〈 50 had shorter TTD (median 18d vs 21d) and TTT (median 30d vs 35d) vs women ≥50 (both p 〈 0.01), and there were no significant differences by race/ethnicity or between women with atypia vs cancer. In multivariate models, however, older age and NH black race were associated with longer TTD and TTT. Conclusions: NC BCCCP meets national quality benchmarks for TTD and TTT. These data also highlight broader opportunities to achieve racial/ethnic parity and improve equity for breast cancer prevention. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 1095-1095
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 1095-1095
    Abstract: 1095 Background: Treatments for metastatic breast cancer (MBC) have significantly improved survival for patients who receive treatment, yet data describing the prognosis for untreated patients is lacking. Therefore, we sought to assess the survival outcomes of patients with de novo MBC who did not receive treatment. Methods: Adults with MBC at diagnosis (clinical M1 or pathologic M1) were selected from the NCDB (2010-2016) and stratified based on receipt of treatment (treated = received at least one treatment; untreated = received no treatments). Differences between patient groups were tested using Chi-square tests for categorical variables and t-tests for continuous variables. Overall survival (OS) was estimated using the Kaplan-Meier method for the overall cohort and stratified by select patient and/or disease characteristics, and groups were compared with log-rank tests. Cox Proportional Hazards models were used to identify factors associated with OS in the untreated MBC subgroup. Results: Of the 53,240 patients with de novo MBC, the median age was 61y (IQR 52-71), and the majority had a comorbidity score of 0 (81.2%). Within this cohort, 49,040 (92.1%) received at least one treatment (treated) and 4,200 (7.9%) had no documented treatments (untreated). Untreated patients were more likely to be older (median 68y vs 61y, p 〈 0.001) and have higher comorbidity scores (p 〈 0.001). Patients with untreated MBC were more likely to have triple negative disease (17.8% vs 12.6%), and a higher disease burden (≥2 metastatic sites: 38.2% untreated vs 29.2% treated, p 〈 0.001). The median unadjusted OS in the untreated subgroup was 2.5mo vs 36.4mo in the treated subgroup (p 〈 0.001). For those who survived at least 1mo post-diagnosis, the median unadjusted OS in the untreated subgroup was 6.9mo vs 37.3mo in the treated subgroup (p 〈 0.001), which increased to 18.6mo and 40.3mo for those who survived at least 3mo post-diagnosis (p 〈 0.001). In the untreated population, unadjusted OS varied by breast cancer subtype (median 3.8mo for HR+/HER2-, vs 2.6mo for HER2+, vs 2.1mo for triple negative, p 〈 0.001) and number of metastatic sites (4.1mo for 1 site, vs 1.8mo for 2 sites, vs 1.1mo for 3 sites, vs 1.2mo for ≥4 sites, p 〈 0.001). After adjustment, variables associated with a worse OS in the untreated cohort included older age, higher comorbidity scores, higher tumor grade, and triple negative (vs HR+/HER2-) tumor subtype (all p 〈 0.05), while the number of metastatic sites was not associated with survival; these same findings were also noted when the analysis was limited to those who survived at least 1mo post-diagnosis. Conclusions: Patients with de novo MBC who do not receive treatment are more likely to be older, present with comorbid conditions, and have clinically aggressive disease. Similar to those who do receive treatment, survival in an untreated population is associated with select patient and disease characteristics. However, the prognosis for untreated MBC is dismal.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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